Background: In the northern hemisphere winter of 2003-04 antigenic variant strains (A/Fujian/411/02 -like) of influenza A H3N2 emerged. Circulation of these strains in the UK was accompanied by an unusually high number of laboratory confirmed influenza associated fatalities in children. This study was carried out to better understand risk factors associated with fatal cases of influenza in children. Methodology/Principal Findings: Case histories, autopsy reports and death registration certificates for seventeen fatal cases of laboratory confirmed influenza in children were analyzed. None had a recognized pre-existing risk factor for severe influenza and none had been vaccinated. Three cases had evidence of significant bacterial co-infection. Influenza strains recovered from fatal cases were antigenically similar to those circulating in the community. A comparison of protective antibody titres in age stratified cohort sera taken before and after winter 2003-04 showed that young children had the highest attack rate during this season (21% difference, 95% confidence interval from 0.09 to 0.33, p = 0.0009). Clinical incidences of influenza-like illness (ILI) in young age groups were shown to be highest only in the years when novel antigenic drift variants emerged. Conclusions/Significance: This work presents a rare insight into fatal influenza H3N2 in healthy children. It confirms that circulating seasonal influenza A H3N2 strains can cause severe disease and death in children in the apparent absence of associated bacterial infection or predisposing risk factors. This adds to the body of evidence demonstrating the burden of severe illness due to seasonal influenza A in childhood.
Bibliographical noteFunding Information:
LEW has received an educational travel grant to attend an American Thoracic Society conference from Altana; DMF has received lecture fees and consultancy fees from Roche in relation to influenza epidemiology, therapeutic management and vaccination; WSB has received financial support for research and consultancy undertaken for Sanofi Pasteur and Crucell relating to the development of new influenza vaccines; the Health Protection Agency receives funding from a variety of influenza vaccine manufacturers for research and development carried out in the laboratory of MCZ. All other authors have no competing interests.